Nirmatrelvir with ritonavir

How it works

Nirmatrelvir inhibits the SARS-CoV-2 main protease (Mpro/3CL protease) to block viral polyprotein processing, while low-dose ritonavir acts purely as a pharmacokinetic booster by inhibiting CYP3A4 to maintain nirmatrelvir concentrations.

Prescribing in practice

• The ritonavir component is a potent CYP3A4 inhibitor and causes numerous serious drug interactions — screen every co-medication (including statins, certain anticoagulants, antiarrhythmics, calcineurin inhibitors and sedatives) before prescribing and consult an interactions resource.
• Must be started as early as possible and within a short defined window from symptom onset to be effective; review the SPC for renal dose adjustment as it is contraindicated in severe renal impairment.
• Treatment course is short and time-limited; counsel on the possibility of symptom rebound after completion.

Monitoring

No routine laboratory monitoring is required for the short course, but renal and hepatic function should be checked at baseline and interacting drugs reviewed throughout.

Counselling the patient

• Take both tablets together and complete the full short course even if you feel better.
• Tell us about every medicine, supplement and herbal product you take, as some must be paused or avoided.
• Some people notice symptoms briefly return after finishing — contact us if you become significantly more unwell.

Evidence & guidelines

The EPIC-HR trial demonstrated reduced risk of COVID-19-related hospitalisation or death in high-risk unvaccinated adults treated early.